Synthesis of Novel Benazepril-Derived Trizole Compounds Assisted by Ultrasound: In Vitro and In Silico Analysis for Potential Anticancer Properties.

Benazepril-based novel trizole derivatives are being explored as potential anticancer agents, designed with an N-substituted 1,2,3-triazole moiety linked to Benazepril's N-1 position via a methylene bridge. An ultrasound irradiated CuAAC method was used to prepare all these compounds and evaluated their anti-proliferative activities against cancer and drug-resistant cell lines. While some of these compounds demonstrated anti-proliferative activity towards leukemic cancer cell line K562, two of them displayed complete inhibitory activity.

A simple and rapid pre-clinical in vivo model reveals comparative cardiotoxicity profiles of kinase inhibitors.

Despite significant success, targeted therapeutics such as kinase inhibitors (KIs) still pose adverse events such as the cardiotoxicity. There is a lot of variation in the type and intensity of cardiotoxicity caused by different KIs and current pre-clinical models are inadequate to predict it. Thus, there is a need to develop more simple and rapid models for screening of novel KIs at the pre-clinical step itself.

AMPK-induced novel phosphorylation of RUNX1 inhibits STAT3 activation and overcome imatinib resistance in chronic myelogenous leukemia (CML) subjects.

Imatinib resistance remains an unresolved problem in CML disease. Activation of JAK2/STAT3 pathway and increased expression of RUNX1 have become one reason for development of imatinib resistance in CML subjects. Metformin has gained attention as an antileukemic drug in recent times.

Large-scale pathogenicity prediction analysis of cancer-associated kinase mutations reveals variability in sensitivity and specificity of computational methods.

Background: Mutations in kinases are the most frequent genetic alterations in cancer; however, experimental evidence establishing their cancerous nature is available only for a small fraction of these mutants.

Aims: Predicition analysis of kinome mutations is the primary aim of this study. Further objective is to compare the performance of various softwares in pathogenicity prediction of kinase mutations.